The experiments proposed will explore further the relationship of naturally occurring neuron death to the normal development of the mammalian CNS. In mammals, this fundamental ontogenetic process has received comparatively less attention than other elemental processes (e.g. neuron formation and migration), and so a significant part of the proposal is devoted to determinations of the timing, magnitude and spatial organization of natural neuron loss in normal rats. The remaining experiments are designed to show some of the controls which operate on young neurons and which control their probability of survival. Neuron losses or gains after experimental manipulations will be determined and related to the normal attrition of cells in the CNS. The goals of the research are to provide a more complete understanding of mammalian development, and ultimately, to provide the basic information necessary for a reasonable approach to clinical problems associated with brain maldevelopment.